Document Detail


The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques.
MedLine Citation:
PMID:  23617731     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate the transfer of Gd-phospholipids among plasma lipoproteins in vitro and in vivo. To determine the basis of this transfer, the roles of phospholipid transfer protein (PLTP) and lipoprotein lipase (LpL) in mediating the migration of Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated that neither was an important factor, suggesting that spontaneous transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally, two independent mouse models were used to quantify the relative contributions of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement by MR. Both sets of results suggested that Gd-DTPA-DMPE originally associated with LDL was about twice as effective as that injected in the form of Gd-HDL, and that some of Gd-HDL's effectiveness in vivo is indirect through transfer of the imaging agent to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a particular type of lipoprotein is complex, and includes its transfer to other lipoprotein species that are then cleared from the plasma into tissues.
Authors:
Alessandra Barazza; Courtney Blachford; Orli Even-Or; Victor A Joaquin; Karen C Briley-Saebo; Wei Chen; Xian-Cheng Jiang; Willem J M Mulder; David P Cormode; Zahi A Fayad; Edward A Fisher
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-05-10
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  24     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-19     Completed Date:  2014-01-20     Revised Date:  2014-06-13    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1039-48     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins E / deficiency
Gadolinium / blood,  chemistry,  diagnostic use*
Lipoproteins, HDL / blood,  chemistry,  diagnostic use*
Magnetic Resonance Angiography*
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Molecular
Molecular Structure
Organometallic Compounds / blood,  chemistry,  diagnostic use*
Plaque, Atherosclerotic / blood,  diagnosis*
Receptors, LDL / deficiency
Grant Support
ID/Acronym/Agency:
EB 009638/EB/NIBIB NIH HHS; EB 012165/EB/NIBIB NIH HHS; HL 084312/HL/NHLBI NIH HHS; HL 098055/HL/NHLBI NIH HHS; P01 HL098055/HL/NHLBI NIH HHS; R00 EB012165/EB/NIBIB NIH HHS; R01 EB009638/EB/NIBIB NIH HHS; R01 HL061814/HL/NHLBI NIH HHS; R01 HL084312/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Lipoproteins, HDL; 0/Organometallic Compounds; 0/Receptors, LDL; AU0V1LM3JT/Gadolinium
Comments/Corrections

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